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Current Opinion in Oncology Sep 2014Primary melanomas originating from the gynaecological tract are rare and aggressive cancers. The 5-year survival is around 10%. The majority of tumours differ from... (Review)
Review
PURPOSE OF REVIEW
Primary melanomas originating from the gynaecological tract are rare and aggressive cancers. The 5-year survival is around 10%. The majority of tumours differ from cutaneous melanomas, which arise from the skin, by developing from melanocytes located in mucosal epithelium. The clinical behaviour, prognosis and the biology of mucosal melanomas are distinct from cutaneous melanomas. In this article, we summarize the current management of melanomas of the gynaecological tract (vulva, vagina, ovary and cervix) and discuss the progress in developing new treatments.
RECENT FINDINGS
The management of mucosal melanomas has not changed substantially over the last decade and the prognosis remains poor. Surgery remains the primary treatment of choice in all localized melanomas of the genital tract. Radiotherapy and chemotherapy are options but have limited success for the majority of women. Activation of c-KIT occurs in vulvar melanomas. Clinical trials of targeted agents are underway.
SUMMARY
As a result of the rarity of gynaecological tract melanomas, challenges associated with their anatomical locations and resistance to conventional radiotherapy and chemotherapy, this group of conditions remain difficult to treat and continue to have a poor prognosis. A greater understanding of the molecular profile of these cancers may provide promising targeted approaches.
Topics: Female; Genital Neoplasms, Female; Humans; Melanoma
PubMed: 25046205
DOI: 10.1097/CCO.0000000000000104 -
PloS One 2023Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that...
Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that MOGS would display unique miR and mRNA expression profiles. The miR and mRNA expression profile in RNA from formalin fixed, paraffin embedded vaginal melanomas (relative to vaginal mucosa) and vulvar melanomas (relative to cutaneous melanoma) were measured with the Nanostring Human miRNA assay and Tumor Signaling mRNA assay. Differential patterns of expression were identified for 21 miRs in vaginal and 47 miRs in vulvar melanoma (fold change >2, p<0.01). In vaginal melanoma, miR-145-5p (tumor suppressor targeting TLR4, NRAS) was downregulated and miR-106a-5p, miR-17-5p, miR-20b-5p (members of miR-17-92 cluster) were upregulated. In vulvar melanoma, known tumor suppressors miR-200b-3p and miR-200a-3p were downregulated, and miR-20a-5p and miR-19b-3p, from the miR-17-92 cluster, were upregulated. Pathway analysis showed an enrichment of "proteoglycans in cancer". Among differentially expressed mRNAs, topoisomerase IIα (TOP2A) was upregulated in both MOGS. Gene targets of dysregulated miRs were identified using publicly available databases and Pearson correlations. In vaginal melanoma, suppressor of cytokine signaling 3 (SOCS3) was downregulated, was a validated target of miR-19b-3p and miR-20a-5p and trended toward a significant inverse Pearson correlation with miR-19b-3p (p = 0.093). In vulvar melanoma, cyclin dependent kinase inhibitor 1A (CDKN1A) was downregulated, was the validated target of 22 upregulated miRs, and had a significant inverse Pearson correlation with miR-503-5p, miR-130a-3p, and miR-20a-5p (0.005 < p < 0.026). These findings support microRNAs as mediators of gene expression in MOGS.
Topics: Humans; Female; Melanoma; Skin Neoplasms; MicroRNAs; Genes, cdc; Vulvar Neoplasms; Suppressor of Cytokine Signaling Proteins
PubMed: 37384650
DOI: 10.1371/journal.pone.0285804 -
Melanoma Research Jun 2024Vulvar melanoma is considered rare, but it is the second most frequent vulvar neoplasm; 2% of melanomas in women arise in the vulvar area. It is important to highlight...
Vulvar melanoma is considered rare, but it is the second most frequent vulvar neoplasm; 2% of melanomas in women arise in the vulvar area. It is important to highlight how the characteristics of vulvar melanoma differentiate it from classic cutaneous melanoma. Vulvar melanoma has different risk factors and clinical and dermoscopic characteristics; moreover, it has a higher recurrence rate and a greater likelihood of multifocality. Here, we present a case of a 44-year-old patient with two primary vulvar melanomas located on opposite sides of her vulva. The lesions were both flat, but they had distinct clinical and dermoscopic appearances. Melanoma of the genital tract is likely the result of a multifocal disorder of the melanocytes within the mucosa that inhabit the perineal squamous epithelium. The risk factors of vulvar melanoma differ from those of classical cutaneous melanomas. Vulvar melanoma occurs in an area shielded from ultraviolet radiation; the primary risk factors include chronic inflammatory disease, genetic susceptibility, irritant agents and viral infections. This case study reveals how a close examination of the genital area is important and how dermoscopy can aid in the differential diagnosis of vulvar lesions. Inspections of the genital area should be particularly thorough if a melanoma is detected there, given the higher risk of multifocality in that part of the body.
PubMed: 38913418
DOI: 10.1097/CMR.0000000000000989 -
Journal of Lower Genital Tract Disease Jul 2020The aims of the study were to evaluate clinicopathologic features, management, and outcomes in vulval melanoma and to review the literature. (Review)
Review
OBJECTIVES
The aims of the study were to evaluate clinicopathologic features, management, and outcomes in vulval melanoma and to review the literature.
MATERIALS AND METHODS
Data were collected retrospectively on patients with vulval melanoma from 2001 to 2017 in 5 gynecological oncology cancer centers (Bristol, Taunton, Truro, Plymouth, and Cheltenham). SPSS software was used for univariate and multivariate statistical analysis. Disease-specific median survival was calculated using Kaplan-Meier curves.
RESULTS
Forty-four patients with vulval melanoma were included, with a median age of 71 years. Forty-three of 44 had wide local excision with full inguinal lymphadenectomy if abnormal lymph nodes. Seven patients had sentinel lymph nodes. However, 2 patients with negative sentinel lymph nodes had distant recurrences within 16 months.On univariate analysis, presence of ulceration (p = .012), perineural invasion (p = .03), and area of lesion (p = .016) were associated with risk of recurrence but only presence of microsatellites (p = .01) was associated with risk of death.There were 31 deaths (70%): 29 (94%) of 31 from melanoma and 28 (64%) of 44 recurrences: 17 local (10 groin, 7 vulval) and 9 distant. Overall median survival was 32.5 months (95% CI, 17.8-46.5 months) and median recurrence-free survival 12.6 months (95% CI, 7.7-17.4 months).
CONCLUSIONS
This retrospective multicenter study highlights the high recurrence rate and poor prognosis of vulval melanoma. Lymph node surgery did not make any difference to recurrence-free survival or overall survival. The presence of microsatellites was associated with a statistically increased risk of death.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Melanoma; Risk Assessment; Skin Neoplasms; Vulvar Neoplasms
PubMed: 32205765
DOI: 10.1097/LGT.0000000000000521 -
Gynecologic Oncology Jul 2018Primary melanomas originating from the gynecological tract are rare and aggressive cancers. The vulva is the most frequent site (70%), followed by vagina and more rarely... (Review)
Review
Primary melanomas originating from the gynecological tract are rare and aggressive cancers. The vulva is the most frequent site (70%), followed by vagina and more rarely by cervix. The clinical outcome of patients with female genital tract melanoma is very poor, with a 5-year overall survival (OS) of 37-50% for vulvar, 13-32% for vaginal, and approximately 10% for cervical melanoma. In this systematic review, we analyzed the pathogenesis and the different factors influencing the prognosis of melanomas of the lower genital tract, with particular emphasis on biologic variables that may influence new therapeutic approaches. We evaluated the different treatment modalities described in the literature, in order to offer a possible algorithm that may help the clinicians in diagnosing and treating patients with these uncommon malignancies.
Topics: Aged; Female; Genital Neoplasms, Female; Humans; Melanoma; Middle Aged; Prognosis; Survival Analysis
PubMed: 29728261
DOI: 10.1016/j.ygyno.2018.04.562 -
Anticancer Research Jun 2018Orbital metastasis of systemic cancer is exceedingly rare. This is a case report of a patient treated for locally recurrent vulvar melanoma who later presented with... (Review)
Review
BACKGROUND/AIM
Orbital metastasis of systemic cancer is exceedingly rare. This is a case report of a patient treated for locally recurrent vulvar melanoma who later presented with unilateral proptosis and was found to have an isolated biopsy-proven extraocular muscle metastasis.
PATIENTS AND METHODS
A 94-year-old female with locally recurrent vulvar melanoma presented with eye discomfort and blurry vision. Patient underwent histopathological, genetic, and imaging studies.
RESULTS
All prior work-up, including brain MRI and PET/CT, was negative for disease elsewhere from local recurrence. Orbital MRI demonstrated a mass involving the extraocular muscle, and immunohistochemistry staining of biopsy was consistent with metastasis. The patient underwent radiation therapy and tolerated treatment well.
CONCLUSION
This is the first reported case of vulvar melanoma with extraocular muscle metastasis. The absence of findings on imaging as part of the staging work-up underscores the importance of considering extraocular muscle (EOM) metastasis as a differential for patients with vulvar melanoma who present with proptosis.
Topics: Aged, 80 and over; Exophthalmos; Female; Humans; Magnetic Resonance Imaging; Melanoma; Muscle Neoplasms; Neoplasm Recurrence, Local; Oculomotor Muscles; Orbital Neoplasms; Treatment Outcome; Vulvar Neoplasms
PubMed: 29848740
DOI: 10.21873/anticanres.12658 -
Current Pharmaceutical Design 2018Technetium (99mTc)-radiolabeled colloids are popular tracers used to map lymphatic vessels and regional lymph nodes (LNs). The regional LN status is a significant... (Review)
Review
Technetium (99mTc)-radiolabeled colloids are popular tracers used to map lymphatic vessels and regional lymph nodes (LNs). The regional LN status is a significant determinant of cancer stage and patient prognosis, and strongly influences treatment. Regional LN dissection has become a part of surgical treatment. However, not all patients with LN involvement benefit from extensive lymphadenectomy in terms of prolonged survival. Moreover, overtreatment of patients with localized disease carries the unnecessary risk of complications. It is believed that sentinel LN biopsy (SLNB) allows to assess the involvement of the most representative LN of the lymphatic basin and to decide on radical LN dissection.99mTc is an easily available radionuclide emitting gamma rays. The value of 99mTc for diagnostic procedures is associated with its relatively short half-life that makes it safe both for patients and medical personnel. A colloid presenting specific physical and biological properties, including optimal particle size, is a carrier for the radionuclide. When administered at the tumor site, a radiocolloid is absorbed by the lymphatics, and the first LN that it gets trapped in is referred to as the sentinel LN (SLN). The radiopharmaceutical must reach the SLN relatively quickly, but its storage within the SLN, and the radionuclide's half-life must be long enough to enable intraoperative imaging and evaluation. SLNB is currently the gold standard in breast cancer and malignant melanoma diagnosis, and is under extensive investigation in gynecological cancers. Here, we provide a historical perspective of the SLN concept and the clinical relevance of SLNB in gynecologic oncology. Moreover, we review the technical aspects of the application of 99mTc-based radiopharmaceuticals in lymphoscintigraphy and intraoperative lymphatic mapping.
Topics: Breast Neoplasms; Female; Humans; Particle Size; Radiopharmaceuticals; Sentinel Lymph Node Biopsy; Surface Properties; Technetium
PubMed: 29766779
DOI: 10.2174/1381612824666180515122150 -
Minerva Ginecologica Dec 2020Vulvar and vaginal melanomas are rare cancers of the female genital tract and account for 1% to 3% of all melanomas diagnosed in women. Due to the rarity of the disease,... (Review)
Review
INTRODUCTION
Vulvar and vaginal melanomas are rare cancers of the female genital tract and account for 1% to 3% of all melanomas diagnosed in women. Due to the rarity of the disease, few data are available on the clinical and pathologic features of these cancers. Furthermore, treatment options are generally based on extrapolations of the information available for the more common cutaneous counterparts. Surgery represents the mainstay of treatment for lower genital tract melanoma. Moreover, the role of sentinel lymph node (SLN) assessment is controversial because no prospective data are available.
EVIDENCE ACQUISITION
Data were collected from Medline, Embase, Web of Sciences and Scopus databases. On July 10, 2020, we used the search comprising the terms "vulvar melanoma," "genital melanoma" and "vulvovaginal melanoma" including only studies in which SLN biopsy was performed.
EVIDENCE SYNTHESIS
Ten retrospective studies have been found. No randomized trials have been reported. The studies included 132 patients while only 63 (47%) undergone SLN. 99mTC with or without blue dye followed by ultrastaging was highly accurate and is currently the gold standard. Mean detection rate was 98.3%. No clear evidence supported the execution of back lymphadenectomy (after SLN mapping), in fact, extrapolating data from cutaneous melanomas of other sites, completion of lymphadenectomy does not confer a melanoma-specific survival advantage.
CONCLUSIONS
Although the small amount of available data, sentinel lymph node procedure is feasible and capable of identifying patients who have occult lymph node metastases. However, the potential role of the sentinel lymph node procedure as an alternative method of lymph node staging in patients with vulvar or vaginal melanoma needs further investigation.
Topics: Female; Humans; Lymph Node Excision; Melanoma; Radiopharmaceuticals; Retrospective Studies; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Technetium; Vaginal Neoplasms; Vulvar Neoplasms
PubMed: 32744452
DOI: 10.23736/S0026-4784.20.04628-6 -
JAMA Dermatology Nov 2020Vulvar melanosis is a common pigmentary change that accounts for most pigmented vulvar lesions. It presents as single or multiple asymptomatic macules or patches of...
IMPORTANCE
Vulvar melanosis is a common pigmentary change that accounts for most pigmented vulvar lesions. It presents as single or multiple asymptomatic macules or patches of varying size and color that may be asymmetric with poorly defined borders. The differential diagnosis of melanocytic lesions includes melanoma, which creates anxiety for patients and the physicians who diagnose the condition and treat the patients.
OBJECTIVE
To evaluate the clinical and dermoscopic features of vulvar melanosis and their changes over time.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study, patients with vulvar melanosis were recruited and followed up in the Department of Dermatology, University of Florence, Florence, Italy, between January 1, 1998, and June 30, 2019. Data on patient characteristics and on both the clinical and dermoscopic features of the vulvar lesions were collected. Each lesion was photographed clinically and dermoscopically at initial evaluation and at annual follow-up visits.
MAIN OUTCOMES AND MEASURES
The clinical, dermoscopic, and histopathologic features of vulvar melanosis and their changes over time.
RESULTS
This cohort study included 129 women (mean age at diagnosis, 46 years [range, 19-83 years]) with vulvar melanosis. A total of 87 patients (67%) with vulvar melanotic lesions were premenopausal, and 84 patients (65%) had received some type of hormone therapy. The most frequent location for vulvar melanosis was the labia minora (55 [43%]), followed by the labia majora (33 [26%]). In 39 of 129 cases (30%), the lesions increased in size and changed color after initial evaluation but ultimately stabilized. No malignant evolution was documented in any patient during a median follow-up of 13 years (range, 5-20 years).
CONCLUSIONS AND RELEVANCE
This study suggests that vulvar melanosis was a benign entity, and changes in lesions over time did not signify malignant transformation. An association between hormonal status and vulvar melanosis may be hypothesized.
Topics: Adult; Aged; Aged, 80 and over; Biopsy; Color; Dermoscopy; Diagnosis, Differential; Disease Progression; Female; Follow-Up Studies; Hormone Replacement Therapy; Humans; Italy; Melanoma; Melanosis; Middle Aged; Mucous Membrane; Photography; Retrospective Studies; Vulva; Vulvar Diseases; Vulvar Neoplasms; Young Adult
PubMed: 32785609
DOI: 10.1001/jamadermatol.2020.2528 -
Archives of Gynecology and Obstetrics Oct 2021
Topics: Diagnosis, Differential; Female; Genitalia; Humans; Melanosis; Vitiligo; Vulvar Diseases
PubMed: 33025087
DOI: 10.1007/s00404-020-05818-6